Wee1 Kinase Inhibitor AZD1775 and Combination Chemotherapy in Treating Children, Adolescents and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia

NCT02791919 | Withdrawn Phase 1 DMC FDA Drug

• 3 other identifiers: NCI-2016-00442ADVL1611UM1CA097452
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I trial studies the side effects and best dose of wee1 kinase inhibitor AZD1775 when given together with fludarabine, cytarabine, and filgrastim (FLAG) combination chemotherapy in treating children, adolescents and young adults with relapsed or refractory acute myeloid leukemia. Wee1 kinase inhibitor AZD1775 may help combination chemotherapy work better by making tumor cells more sensitive to the drugs. Drugs used in chemotherapy, such as fludarabine and cytarabine, may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA), which in turn stops the tumor from growing. Giving wee1 kinase inhibitor AZD1775 and FLAG chemotherapy may work better in treating patients with acute myeloid leukemia.

Conditions

CNS 2a; CNS 2b; CNS 2c; CNS1; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events graded according to National Cancer Institute (NCI) CTCAE version 4.0

  Day 28 of course 1

• MTD of wee1 kinase inhibitor AZD1775 and combination chemotherapy based on incidence of dose limiting toxicity (DLT) assessed by Common Terminology Criteria for Adverse Events version 4

  Day 28 of course 1

• Pharmacokinetic parameters of wee1 kinase inhibitor AZD1775 and combination chemotherapy

  Plasma will be collected and wee1 kinase inhibitor AZD1775 concentrations will be analyzed.

  Pre-dose, 1, 2, 4, 6, 8, and 24 hours on day 1, pre-dose on day 4, and pre-dose, 1, 2, 4, 6, and 8 hours of day 5 of course 1

Secondary Outcomes (6)

• Complete Remission

  Day 28 of course 1

• CR with Incomplete Blood Count Recovery (CRi)

  Day 28 of course 1

• CR With Partial Recovery of Platelet Count

  Day 28 of course 1

• Overall response

  Day 28 of course 1

• Partial response (PR)

  Day 28 of course 1

Study Arms (1)

Treatment (AZD1775, FLAG chemotherapy)

EXPERIMENTAL

Patients receive filgrastim IV or SC daily, fludarabine intravenously IV over 30 minutes, cytarabine IV over 1-3 hours and wee1 kinase inhibitor AZD1775 PO on days 1-5. Patients who meet criteria for CR, CRp or PR may receive a second course of therapy. Courses repeat every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Drug: Cytarabine; Biological: Filgrastim; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: WEE1 Inhibitor AZD1775

Interventions

Cytarabine DRUG

Given IV or IT

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (AZD1775, FLAG chemotherapy)

Filgrastim BIOLOGICAL

Given IV or SC

Also known as: Filgrastim XM02, Filgrastim-sndz, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tbo-filgrastim, Tevagrastim, Zarxio

Treatment (AZD1775, FLAG chemotherapy)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (AZD1775, FLAG chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (AZD1775, FLAG chemotherapy)

Pharmacological Study OTHER

Correlative studies

Treatment (AZD1775, FLAG chemotherapy)

WEE1 Inhibitor AZD1775 DRUG

Given PO

Also known as: AZD-1775, AZD1775, MK-1775, MK1775

Treatment (AZD1775, FLAG chemotherapy)

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have had histologic verification of AML at original diagnosis; AML is defined according to World Health Organization (WHO) classification with \>= 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease
• Relapsed patients:
• Second or greater relapse OR
• AML in first relapse AND has received \>= 450 mg/m\^2 daunorubicin equivalents
• NOTE: for the purposes of determining eligibility for this protocol, the following cardiotoxicity multipliers will be used to determine daunorubicin equivalents:
• Doxorubicin: 1
• Mitoxantrone: 3
• Idarubicin: 3
• Epirubicin: 0.5
• Refractory patients:
• Patients must have received at least two attempts at remission induction, which may consist of up to two different therapy courses; Children's Oncology Group (COG) AAML1031 de novo therapy including induction I and induction II is one remission attempt
• Patients must have the status of central nervous system (CNS)1 or CNS2 only, and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy
• Patients must have a body surface area \>= 0.35 m\^2 at the time of study enrollment
• Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50 for patients =\< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

You may not qualify if:

• Myelosuppressive chemotherapy:
• Must be 14 days after the last dose of myelosuppressive chemotherapy (excluding hydroxyurea)
• Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of therapy
• Intrathecal cytotoxic therapy:
• No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone
• At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection
• Intrathecal cytarabine given at the time of diagnostic lumbar puncture (LP) to evaluate for relapse prior to study enrollment is allowed
• Biologic (anti-neoplastic agent):
• At least 7 days since the completion of therapy with a biologic agent such retinoids, or DLI (donor lymphocyte infusion without conditioning)
• Note: for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which acute adverse events are known to occur
• Interleukins, Interferons and Cytokines (other than hematopoietic growth factors):
• \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Antibodies:
• \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
• Radiation therapy (RT):

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Filgrastim; Granulocyte Colony-Stimulating Factor; fludarabine phosphate; adavosertib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Maureen O'Brien

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2016
• First Posted: June 7, 2016
• Study Start: May 25, 2017
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2019
• Last Updated: May 3, 2017

Record last verified: 2017-05